Pharmaceutical composition including dutasteride and capsule formulation comprising the same

ABSTRACT

The present disclosure relates to a pharmaceutical composition comprising dutasteride and propylene glycol monolaurate, and a capsule formulation comprising the same.

TECHNICAL FIELD

The present disclosure relates to a pharmaceutical compositioncomprising dutasteride, and a capsule formulation comprising the same.

BACKGROUND ART

U.S. Pat. No. 5,565,467 discloses that dutasteride (chemical name:17β-N-(2,5-bis(trifluoromethyl))phenylcarbamoyl-4-aza-5α-androst-1-en-3-one)of the following Formula (I), a 5-alpha reductase inhibitor, is capableof being used in treating benign prostate hyperplasia, prostate cancerand male pattern alopecia (androgenetic alopecia).

Dutasteride is commercially available as AVODART® soft gelatin capsulewhich contains 0.5 mg of dutasteride dissolved in 349.5 mg of a mixtureof mono- and di-glyceride of caprylic/capric acid and butylated hydroxytoluene (BHT).

However, in order to fill the active ingredient, dutasteride into thesoft gelatin capsule, a large amount of oils and surfactants arerequired to be used, leading to an increase in the size of the capsule.The large-sized capsule may cause low patient compliance due topatient's inability or unwillingness to swallow the large-sizedformulations. In particular, considering that the great majority ofbenign prostate hyperplasia patients is elderly patients, the large sizeof the dutasteride capsule leads to disadvantages in that taking suchlarge capsule is very inconvenient for elderly patients and thus patientcompliance is low.

DISCLOSURE OF INVENTION Technical Problem

To solve this problem, the present disclosure provides a pharmaceuticalcomposition containing dutasteride having improved stability, patientcompliance, dissolution rate and bioavailability, and a capsuleformulation comprising the same.

Aspects of the present disclosure are not limited to the technicalproblem described above, and other technical problems that are notdescribed will be clear to those skilled in the art from the descriptionprovided below.

Solution to Problem

In one aspect, the present disclosure relates to a pharmaceuticalcomposition comprising dutasteride of the following Formula (I) andpropylene glycol monolaurate:

In another aspect of the present disclosure, the pharmaceuticalcomposition further comprises a surfactant having a hydrophile-lypophilebalance (HLB) value of greater than or equal to 10 and less than orequal to 30.

According to one embodiment of the present pharmaceutical composition,the content of dutasteride is greater than or equal to 0.1% by weightand less than or equal to 3.0% by weight, the content of propyleneglycol monolaurate is greater than or equal to 84.0% by weight and lessthan or equal to 99.8% by weight, and the content of the surfactanthaving a HLB value of greater than or equal to 10 and less than or equalto 30 is greater than or equal to 0.1% by weight and less than or equalto 15.0% by weight based on the total weight of the pharmaceuticalcomposition.

According to another embodiment of the present pharmaceuticalcomposition, the surfactant having a HLB value of greater than or equalto 10 and less than or equal to 30 is selected from the group consistingof polyoxyl castor oil, polyoxyl sorbitan fatty acid ester, polyoxylstearic acid, polyoxyl glyceride, a polyoxyethylene-polyoxypropylenecopolymer and any combination thereof.

According to another embodiment of the present pharmaceuticalcomposition, the pharmaceutical composition further comprises one ormore of a second surfactant having a hydrophile-lypophile balance (HLB)value of greater than or equal to 6 and less than or equal to 9, and aco-surfactant.

According to another embodiment of the present pharmaceuticalcomposition, the pharmaceutical composition further comprisespharmaceutically acceptable excipients.

In another aspect, the present disclosure relates to a capsuleformulation comprising the pharmaceutical composition.

According to one embodiment of the present capsule formulation, thepharmaceutical composition is a clear solution which can beself-emulsified when digested or contact with water.

Other embodiments of the present disclosure are included in the detaileddescription and the drawings.

Advantageous Effects of Invention

The present disclosure is capable of providing a pharmaceuticalcomposition comprising dutasteride having improved stability, patientcompliance, dissolution rate and bioavailability, and a capsuleformulation including the same.

Effects of the present disclosure are not limited to the effectsillustrated above, and more various effects are included in the presentspecification.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a picture comparing a capsule prepared according to oneembodiment of the present disclosure and a commercially-availableAVODART® capsule.

FIG. 2 is a graph of bioavailability comparison tests of comparativeexamples and an example of the present disclosure.

MODE FOR THE INVENTION

Advantages and characteristics of the present disclosure, and methods ofaccomplishing the same may be understood more readily by reference tothe following detailed description of embodiments. However, the presentdisclosure may be embodied in many different forms, and should not beconstrued as being limited to the embodiments set forth herein. Rather,these embodiments are provided so that this disclosure is thorough andcomplete and fully conveys the concept of the invention to those skilledin the art, and the present disclosure is only defined by the scope ofthe appended claims.

In the present specification, a singular form also includes a pluralform unless particularly mentioned otherwise in the sentence, and“comprise(s)” and/or “comprising” do not exclude the presence oraddition of one or more other constituents.

A pharmaceutical composition according to one embodiment of the presentdisclosure comprises dutasteride of the following Formula (I) andpropylene glycol monolaurate.

The pharmaceutical composition according to one embodiment of thepresent disclosure may further comprise a surfactant.

In the present pharmaceutical composition, propylene glycol monolaurateand a surfactant may perform as a solubilizer which solubilizesdutasteride that is a pharmaceutically active ingredient and has poorsolubility, and increases its solubility.

The pharmaceutical composition according to one embodiment of thepresent disclosure is a clear solution which can be self-emulsified whendigested or contact with water.

In the pharmaceutical composition according to one embodiment of thepresent disclosure, the solubility of dutasteride may be increased byusing propylene glycol monolaurate or a mixture of propylene glycolmonolaurate and a surfactant as a solubilizer of dutasteride.

As a result, the size of the capsule formulation according to oneembodiment of the present disclosure becomes smaller compared toAVODART® and is capable of improving patient compliance compared toAVODART®, and improving dissolution rate and bioavailability. FIG. 1 isa picture comparing a capsule prepared according to one embodiment ofthe present disclosure and a commercially-available AVODART® capsule.When referring to FIG. 1, it is identified that the capsule formulationaccording to one embodiment of the present disclosure (right, size of 2oval) is smaller than the AVODART® capsule (left, size of 6 oblong).

Besides, propylene glycol monolaurate is capable of improving thestability of the pharmaceutical composition according to one embodimentof the present disclosure.

Hereinafter, the pharmaceutical composition according to one embodimentof the present disclosure will be described in detail with reference toexamples and comparative examples.

Propylene glycol monolaurate is favorably mixed with a surfactant andincreases the solubility of dutasteride, and therefore, may form astable emulsion in water. In addition, propylene glycol monolaurate mayenhance the stability of dutasteride.

Test Example 1 is a test result comparing the solubility of dutasteridedepending on the types of oil. As identified in Table 1 of Test Example1, dutasteride is not favorably soluble in general oil such as soybeanoil and castor oil, whereas in propylene glycol monolaurate used in thepresent disclosure, the solubility of dutasteride is higher by 10 timesor greater compared to the solubility in general oil.

As shown in Test Examples 2 and 3, the stability of dutasteride in oilwas measured by determining whether degradation products are generatedwhen stored under an accelerated stress condition (40° C., 75% RH) andwhen stored under a stress condition (50° C., 95% RH). When usingcaprylic/capric acid mono- and di-glyceride oil used in a commerciallyavailable AVODART® capsule, many degradation products were generatedunder both the accelerated and stress conditions. However, degradationproducts were not generated in propylene glycol monolaurate oil whenstored under an accelerated condition for 4 weeks. Further, even whenstored under a stress condition for 4 weeks, it was seen thatsignificantly smaller amounts of degradation products were producedcompared to caprylic/capric acid mono- and di-glyceride.

In addition, as identified in a stability test (Test Example 3), amixture of propylene glycol monocaprylate with a surfactant showsfavorable solubility for dutasteride, but significantly low stability ofdutasteride. However, it was identified that both solubility andstability of dutasteride was very superior in a mixture of propyleneglycol monolaurate with a surfactant.

Based on the solubility and stability tests, it was identified thatpropylene glycol monolaurate is capable of enhancing solubility andstability of dutasteride in the pharmaceutical composition of thepresent disclosure.

Meanwhile, the surfactant of the present disclosure performs a role ofenhancing the solubility of dutasteride and forming a stable emulsion bystably emulsifying propylene glycol monolaurate in water. The surfactantof the present disclosure may comprise a first surfactant having ahydrophile-lypophile balance (HLB) value of greater than or equal to 10and less than or equal to 30, and optionally one or more of a secondsurfactant having a HLB value of greater than or equal to 6 and lessthan or equal to 9 and a co-surfactant.

For example, the surfactant may be the first surfactant, or a mixture ofthe first surfactant and the second surfactant, or a mixture of thefirst surfactant and the co-surfactant. The second surfactant mayperform a role of maintaining stability in water by assistingsolubilization of dutasteride, and the co-surfactant may perform a roleof assisting solubilization of dutasteride. The second surfactant andthe co-surfactant are supplements assisting the role of the firstsurfactant, and the surfactant essentially consists of the firstsurfactant.

In this regard, according to the results of phase equilibrium study,when using, for example, a mixture comprising polyoxyl 40 hydrogenatedcastor oil and poloxamer 124 as the surfactant, the mixture of polyoxyl40 hydrogenated castor oil and poloxamer 124 were well blended withpropylene glycol monolaurate, thereby forming a stable emulsion inwater.

Examples of the first surfactant may include one or more of polyoxylcastor oil, polyoxyl sorbitan fatty acid ester, polyoxyl stearic acid,polyoxyl glyceride and a poly-oxyethylene-polyoxypropylene copolymer,including, but not limited to, poly-oxyethylene 35 castor oil,polyethylene glycol (PEG) 6 glyceryl carpylate/caprate, PEG 40hydrogenated castor oil, poloxamer 124, poloxamer 188, and PEG 15hydroxystearate. Examples of the second surfactant may include, but notlimited to, sorbitan fatty acid ester, for example, polysorbate 80,polysorbate 60, and polysorbate 40. Examples of the co-surfactant mayinclude, but not limited to, diethylene glycol monoethyl ether,propylene glycol, polyethylene glycol and the like, for example,Transcutol, PEG 600, and PEG 300.

When the pharmaceutical composition according to one embodiment of thepresent disclosure includes dutasteride, propylene glycol monolaurateand a surfactant, the dutasteride content may be greater than or equalto 0.1% by weight and less than or equal to 3.0% by weight based on thetotal weight of the pharmaceutical composition, and the propylene glycolmonolaurate content may be greater than or equal to 84.0% by weight andless than or equal to 99.8% by weight based on the total weight of thepharmaceutical composition, and the surfactant content may be greaterthan or equal to 0.1% by weight and less than or equal to 15.0% byweight based on the total weight of the pharmaceutical composition.

The content of dutasteride may be 0.1 to 3.0% by weight, preferably 0.1to 1.0% by weight, more preferably 0.2 to 0.6% by weight based on thetotal weight of the pharmaceutical composition. When the dutasteridecontent is less than 0.1% by weight based on the total weight of thepharmaceutical composition, the solubilizer content relativelyincreases, thereby leading to an increase in the mass of the capsule,which is disadvantageous in that taking the medicine is inconvenient.The dutasteride content of greater than 3.0% by weight based on thetotal weight of the pharmaceutical composition is disadvantageous inthat it is difficult to dissolve dutasteride.

The content of propylene glycol monolaurate may be 84.0 to 99.8% byweight, preferably 90.0 to 99.0% by weight, more preferably 95.0 to98.0% by weight based on the total weight of the pharmaceuticalcomposition. When the propylene glycol monolaurate content is less than84.0% by weight based on the total weight of the pharmaceuticalcomposition, dutasteride is not sufficiently dissolved, which may leadto a disadvantage of precipitation. When the propylene glycolmonolaurate content is greater than 99.8% by weight based on the totalweight of the pharmaceutical composition, the amount of the surfactantused decreases, which may cause decline in the emulsifying ability ofthe formulation.

The content of the first surfactant may be greater 0.1 to 15.0% byweight, preferably 1.0 to 10% by weight, more preferably 2.0 to 5.0% byweight based on the total weight of the pharmaceutical composition. Whenthe first surfactant content is less than 0.1% by weight based on thetotal weight of the pharmaceutical composition, the emulsion formingability may decline. When the first surfactant content is greater than15.0% by weight based on the total weight of the pharmaceuticalcomposition, the capsule is hardened and may cause decline in thestability of the formulation and the stability of dutasteride.

Meanwhile, the pharmaceutical composition according to one embodiment ofthe present disclosure may further comprise pharmaceutically acceptableexcipients within the scope that does not interfere with the purpose ofthe present disclosure. The pharmaceutically acceptable excipients maybe selected from one or more of antioxidants, colorants, andpreservatives. Examples of the antioxidants may include butylatedhydroxy toluene (BHT), butylated hydroxy anisole (BHA) and the like.

The pharmaceutical composition according to one embodiment of thepresent disclosure may be prepared by uniformly mixing dutasteride,propylene glycol monolaurate and a surfactant.

The capsule formulation according to one embodiment of the presentdisclosure may be a soft capsule formulation or a hard capsuleformulation, and may be prepared by filling the soft capsule base or thehard capsule base with a homogeneously mixed solution of dutasteride,propylene glycol monolaurate and a surfactant according to a method forpreparing a capsule formulation known in the art.

The amount of the mixed solution of dutasteride, propylene glycolmonolaurate and a surfactant being filled in a capsule formulation canbe 92 mg to 185 mg, preferably 100 mg to 150 mg, more preferably 110 mg.The capsule formulation of the present disclosure can be prepared insize 2 oval (minims: 1.5-1.8, cc: 0.092-0.111), size 3 oval (minims:2.4-3.0, cc: 0.148-0.185), size 3 oblong (minims: 2.3-3.0, cc:0.142-0.185), size 4 oblong (minims: 3.0-4.0, cc: 0.185-0.246) and thelike. The size of the capsule formulation according to one embodiment ofthe present disclosure is smaller compared to size 6 oblong of AVODART®(minims: 5.0-6.0, cc: 0.308-0.370). Thus, the capsule formulation of thepresent disclosure is capable of improving patient compliance comparedto AVODART®.

The following test examples indicate that the pharmaceutical compositionaccording to one embodiment of the present disclosure and a capsuleformulation including the same exhibit excellent stability, excellentpatient compliance, excellent dissolution rate, excellentbioavailability and the like compared to comparative examples.

Hereinafter, the present disclosure will be described in detail withreference to examples so that those having average knowledge in thetechnology field to which the present disclosure belongs may readilycarry out the invention. However, the present disclosure may be embodiedin various different forms and is not limited to the examples describedherein.

Example 1

To a 3 L preparation container equipped with a stirrer, 1,040 g ofpropylene glycol monolaurate was added, and while stirring, 5 g ofdutasteride was slowly added thereto and completely dissolved. 33 g ofpolyoxyl 40 hydrogenated castor oil and 22 g of poloxamer 124 were addedthereto, and the resultant mixture was stirred to prepare a solubilizedcomposition. A soft capsule shell was prepared using gelatin, aplasticizer and the like according to a method known in the art. Afterfilling a size 2 oval soft capsule with 110 mg of the preparedsolubilized composition using a rotary-type automatic filler, a softcapsule formulation for oral administration was prepared after goingthrough drying and sorting processes.

Examples 2 to 8

To a 500 mL preparation container equipped with a stirrer, 104 g ofpropylene glycol monolaurate was added, and while stirring, 0.5 g ofdutasteride was slowly added thereto and completely dissolved.Surfactants were added thereto in the amounts specified in the followingTable 1, and after stirring and thoroughly mixing the resultant mixture,0.01 g of butylated hydroxy toluene was added thereto and dissolved toprepare a solubilized composition. A soft capsule shell was preparedusing a method known in the art as in Example 1. After filling a size 2oval soft capsule with 110 mg of the prepared solubilized compositionusing a rotary-type automatic filler, a soft capsule formulation fororal administration was prepared after going through drying and sortingprocesses.

TABLE 1 Content Example 2 Example 3 Example 4 Example 5 Example 6Example 7 Example 8 Dutasteride 0.5 g 0.5 g 0.5 g 0.5 g 0.5 g 0.5 g 0.5g Propylene Glycol 104 g 104 g 104 g 104 g 104 g 104 g 104 g MonolaurateButylated Hydroxy 0.01 g 0.01 g 0.01 g 0.01 g 0.01 g 0.01 g 0.01 gToluene Polyoxyethylene 35 5.49 g 3.3 g Castor Oil PEG 40 Hydrogenated5.49 g 3.3 g Castor Oil Polysorbate 80 5.49 g PEG 6 Glyceryl 5.49 gCarpylate/Caprate PEG 15 5.49 g Hydroxystearate Poloxamer 124 2.19 g2.19 g

Examples 9 to 15

To a 500 mL preparation container equipped with a stirrer, propyleneglycol monolaurate was added in the amount specified in the followingTable 2, and while stiffing, 0.5 g of dutasteride was slowly addedthereto and completely dissolved. Surfactants were added thereto in theamounts specified in the following Table 2, and after stiffing andthoroughly mixing the resultant mixture, butylated hydroxy toluene wasadded thereto and dissolved to prepare a solubilized composition. A softcapsule shell was prepared in the same manner as in Example 1. Afterfilling a size 2 oval soft capsule with 110 mg of the preparedsolubilized composition using a rotary-type automatic filler, a softcapsule formulation for oral administration was prepared after goingthrough drying and sorting processes.

TABLE 2 Content Example 9 Example 10 Example 11 Example 12 Example 13Example 14 Example 15 Dutasteride 0.5 g 0.5 g 0.5 g 0.5 g 0.5 g 0.5 g0.5 g Propylene Glycol 106 g 105 g 104 g 106 g 108 g 105 g 105 gMonolaurate Butylated Hydroxy 0.01 g 0.01 g 0.01 g 0.01 g 0.01 g 0.01 g0.01 g Toluene Polyoxyethylene 35 3.49 g — — — 1.3 g 2.3 g 2.3 g CastorOil PEG 40 Hydrogenated — 4.49 g — — — — — Castor Oil PEG 6 Glyceryl — —2.49 g — — — — Carpylate/Caprate PEG 15 — — — 3.49 g — — —Hydroxystearate Poloxamer 124 — — 3 g — 0.19 g — — Poloxamer 188 — — — —— 2.19 g — Transcutol — — — — — — 2.19 g

Example 16

To a 0.5 L preparation container equipped with a stirrer, 104 g ofpropylene glycol monolaurate was added, and while stirring, 0.5 g ofdutasteride was slowly added thereto and completely dissolved. 33 g ofpolyoxyl 40 hydrogenated castor oil and 22 g of lecithin were addedthereto, and the resultant mixture was stirred to prepare a solubilizedcomposition. A size 4 oblong gelatin hard capsule was filled with 110 mgof the solubilizer composition to prepare a hard capsule formulation fororal administration.

Test Example 1

In order to measure the solubility of dutasteride in oil, the solubilityof dutasteride in soybean oil, castor oil, propylene glycol dicaprylate,propylene glycol dicaprate and propylene glycol monolaurate wasmeasured. In a 10 mL vial, a magnetic bar was placed. After 3 mL of theoil was added thereto, approximately 100 mg of dutasteride was addedthereto while stirring under a room temperature (25° C.) condition, andthe resultant mixture was stirred with 500 rpm or higher. After stiffingfor 24 hours, 1 mL of the resultant mixture was taken and separatedusing a centrifuge, and only the supernatant was taken to quantify theamount of dutasteride dissolved in the oil using liquid chromatography.As for the solubility in each oil obtained from the test results,propylene glycol monolaurate exhibited higher solubility by 10 times orgreater compared to other tested oils, as shown in Table 3.

TABLE 3 Solubility of Dutasteride Depending on Oil Type Oil Solubilityof Dutasteride (mg/mL) Soybean Oil 0.00 Castor Oil 1.50 Propylene GlycolDicaprylate 1.13 Propylene Glycol Dicaprate 0.77 Propylene GlycolMonolaurate 10.43

Test Example 2: Test I on Stability of Pharmaceutical CompositionDepending on Oil Type

In order to identify the stability of dutasteride in propylene glycolmonolaurate exhibiting the excellent solubility in the solubilityevaluation, the stability of dutasteride in mono-di-glyceride ofcaprylic/capric acid used as an oil phase of AVODART®, an existingcommercially-available formulation, was compared under a stresscondition (50° C., 95% RH) and an accelerated condition (40° C., 75%RH). As samples used in the comparison test, a sample dissolving 1.0 mgof dutasteride in 10.0 mg of propylene glycol monolaurate and stored ina transparent vial, and a sample dissolving 1.0 mg of dutasteride in10.0 mg of caprylic/capric acid mono-di-glyceride and stored in atransparent vial were used. The percentage of degradation products withrespect to dutasteride, a main substance, was calculated and summarizedin the following Table 4.

TABLE 4 Evaluation I on Stability of Dutasteride Depending on Oil TypeAmount of Degradation Products (%) Oil Storage Condition After 4 WeeksPropylene Glycol Accelerated Condition None Monolaurate (40° C., 75% RH)Stress Condition 0.32% (50° C., 95% RH) Caprylic/Capric AcceleratedCondition 0.94% Acid Mono-Di- (40° C., 75% RH) Glyceride StressCondition 1.75% (50° C., 95% RH)

As can be identified from Table 4, the stability of dutasteride inpropylene glycol monolaurate was more superior compared to thecaprylic/capric acid mono-di-glyceride in the week 4 under anaccelerated condition (40° C., 75% RH) and a stress condition (50° C.,95% RH).

Test Example 3

A stability test on the pharmaceutical composition of the comparativeexample dissolving 0.5 mg of dutasteride in a mixture of 95 mg ofpropylene glycol monocaprylate and 5 mg of polyoxyl 35 castor oil andstored in a transparent vial, and the pharmaceutical composition of theexample including dutasteride, propylene glycol monolaurate and polyoxyl35 castor oil was carried out by identifying the generation ofdegradation products under an accelerated condition (40° C., 75% RH) anda stress condition (50° C., 95% RH). As shown in the following Table 5,it was seen that the mixture of propylene glycol monolaurate and asurfactant secured the stability of dutasteride unlike mixtures ofsurfactant with other oils such as propylene glycol monocaprylate.

TABLE 5 Evaluation II on Stability of Dutasteride in Mixture of Oil andSurfactant Amount of Degradation Products (%) Oil Surfactant After 3Weeks After 4 Weeks Propylene Glycol Polyoxyl 35 None None MonolaurateCastor Oil Propylene Glycol Polyoxyl 35 6.2% 12.1% Monocaprylate CastorOil

Test Example 4: Stress Test on Stability in Soft Capsule

In order to evaluate the stability in a soft capsule formulation, thesoft capsule formulation of Example 1 was transparent PVDC blisterpacked, and then each stored under each of various stress conditions(light: 300 W/m², temperature: 50° C., or humidity: 95% RH) to identifythe presence of degradation products.

TABLE 6 Results of Stress Test on Stability in Soft Capsule FormulationCondition Light: Temperature: Humidity: 300 W/m² 50° C. 95% RH Example 16 Hours: None3 1 Week: None2 1 Week: None2 Days: None Weeks: None3Weeks: None3 Weeks: None4 Weeks: None4 Weeks: None Weeks: None

Test Example 5: In Vivo Bioavailability Comparison Test on Beagle Dog

A bioavailability comparative evaluation in beagle dogs was carried outusing Example 1, Comparative Example 1 and Comparative Example 2. Beagledogs were used as the in vivo test animal. Four beagle dogs were usedfor Comparative Example 1, a commercially-available formulation, andthree beagle dogs were used each for Example 1 and Comparative Example2. 0.5 mg of dutasteride and 40 mL of drinking water were orallyadministered to each beagle dogs starved in advance.

After the oral administration, blood was collected at times after 0hours, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours,24 hours, 48 hours, 72 hours and 144 hours had passed, and theconcentrations of dutasteride in the blood were analyzed usingHPLC/Ms/Ms.

As Comparative Example 1, a currently commercially-available AVODART®0.5 mg soft capsule containing 0.5 mg of dutasteride was used. AsComparative Example 2, a soft capsule was prepared so as to contain 0.5mg of dutasteride per 1 capsule as in Example 1 except that thesolubilized composition was prepared by placing and dissolving 0.5 g ofdutasteride in 104 g of propylene monocaprylate, 3.3 g of polyoxyl 35castor oil and 2.19 g of poloxamer 124 while stirring.

As can be identified in the following Table 7 and FIG. 2, Example 1 hadmore improved bioavailability compared to Comparative Example 1 andComparative Example 2. Particularly, Example 1 had a smaller formulationsize, but exhibited improved bioavailability compared to AVODART® ofComparative Example 1.

TABLE 7 Results of in vivo Bioavailability Test on Beagle Dog AUC_(t)(ng/mL × hr)¹⁾ C_(max) (ng/mL)²⁾ T_(max) (hr)³⁾ Example 1 4020.90 ±702.78  63.04 ± 10.77 0.67 ± 0.29 Comparative 3654.08 ± 753.09 47.08 ±8.39 3.25 ± 1.50 Example 1 Comparative 3008.46 ± 62.97  41.30 ± 1.922.00 ± 1.73 Example 2 ¹⁾Area under Curve of Concentration in Blood up to144 Hours after Administration ²⁾Maximum Concentration in Blood ³⁾Timeat Maximum Concentration in Blood

Test Example 6: Dissolution Test

A dissolution evaluation was carried out on the soft capsule formulationof Example 1 and the commercially-available AVODART® 0.5 mg soft capsuleof Comparative Example 1. The dissolution test was carried out inaccordance with Method 2 of the dissolution test method in the KoreanPharmacopoeia, 10th edition using a 0.1% aqueous lauryl sodium sulfatesolution as the eluent and a rotation speed of 50 rpm. As shown in thefollowing Table 8, it was identified that the dissolution rate inExample 1 was more superior compared to the AVODART® of ComparativeExample 1.

TABLE 8 Result of Evaluation on Dissolution Example 1 ComparativeExample 1  5 Minutes 26.5% 0.0% 10 Minutes 56.1% 36.4% 15 Minutes 68.3%49.5% 30 Minutes 87.1% 55.6%

The test examples and the like are for illuminating the presentdisclosure, and technological ideas of the present disclosure are notlimited to the test examples and the like described above. Substitutionof equivalents, addition or deletion of other constituents, and the likewithin the scope of not impairing the technological ideas of the presentdisclosure are still incorporated into the present specification andconstitute the contents of the present disclosure.

1. A pharmaceutical composition comprising dutasteride of the followingFormula (I) and propylene glycol monolaurate:


2. The pharmaceutical composition of claim 1, further comprising asurfactant having a hydrophile-lypophile balance (HLB) value of greaterthan or equal to 10 and less than or equal to
 30. 3. The pharmaceuticalcomposition of claim 2, wherein the content of dutasteride is greaterthan or equal to 0.1% by weight and less than or equal to 3.0% byweight, the content of propylene glycol monolaurate is greater than orequal to 84.0% by weight and less than or equal to 99.8% by weight, andthe content of the surfactant having a HLB value of greater than orequal to 10 and less than or equal to 30 is greater than or equal to0.1% by weight and less than or equal to 15.0% by weight based on thetotal weight of the pharmaceutical composition.
 4. The pharmaceuticalcomposition of claim 2, wherein the surfactant having a HLB value ofgreater than or equal to 10 and less than or equal to 30 is selectedfrom the group consisting of polyoxyl castor oil, polyoxyl sorbitanfatty acid ester, polyoxyl stearic acid, polyoxyl glyceride, apolyoxyethylene-polyoxypropylene copolymer and any combination thereof.5. The pharmaceutical composition of claim 2, further comprising one ormore of a second surfactant having a hydrophile-lypophile balance (HLB)value of greater than or equal to 6 and less than or equal to 9, and aco-surfactant.
 6. The pharmaceutical composition of claim 2, furthercomprising pharmaceutically acceptable excipients.
 7. A capsuleformulation comprising the pharmaceutical composition of claim
 1. 8. Thecapsule formulation of claim 7, wherein the pharmaceutical compositionis a clear solution which can be self-emulsified when digested orcontact with water.
 9. A capsule formulation comprising thepharmaceutical composition of claim
 2. 10. The capsule formulation ofclaim 9, wherein the pharmaceutical composition is a clear solutionwhich can be self-emulsified when digested or contact with water.
 11. Acapsule formulation comprising the pharmaceutical composition of claim3.
 12. The capsule formulation of claim 11, wherein the pharmaceuticalcomposition is a clear solution which can be self-emulsified whendigested or contact with water.
 13. A capsule formulation comprising thepharmaceutical composition of claim
 4. 14. The capsule formulation ofclaim 13, wherein the pharmaceutical composition is a clear solutionwhich can be self-emulsified when digested or contact with water.
 15. Acapsule formulation comprising the pharmaceutical composition of claim5.
 16. The capsule formulation of claim 15, wherein the pharmaceuticalcomposition is a clear solution which can be self-emulsified whendigested or contact with water.
 17. A capsule formulation comprising thepharmaceutical composition of claim
 6. 18. The capsule formulation ofclaim 17, wherein the pharmaceutical composition is a clear solutionwhich can be self-emulsified when digested or contact with water.